There is a rapidly growing translational research effort to understand the brain mechanisms of dysfunction in neurodevelopmental disorders such as fragile X syndrome (FXS), Down syndrome (DS), and other conditions that cause intellectual disabilities (ID). Evidence from the animal models of these syndromic forms of disability documents that targeted treatments have strong potential to normalize the neurobiological, behavioral, and perhaps cognitive abnormalities associated with these conditions in humans. This groundbreaking work has led to many controlled clinical trials already underway, and many more now in the planning stages. However, virtually no developmentally appropriate, well-validated, sensitive and reliable cognitive measures suitable for tracking treatment response are available for individuals with ID. Indeed it could be argued that lack of timely development of such measures has significantly slowed translation of targeted treatments and could result in incorrect interpretation of such trial results, compromising development efforts for targeted treatments aimed at ID syndromes. In response to this urgent need, the primary aim of the proposed project is to validate a set of cognitive measures of executive function, processing speed, episodic memory, language, and attention for use as outcome measures for individuals with ID, with a primary initial focus on fragile X and Down syndromes. This cognitive battery was initially developed by the NIH Neuroscience Blueprint Toolbox consortium for the general population for ages of 3 to 89 years, and in the current project will be validated and modified as necessary for those with ID. Furthermore, a longitudinal study of these and other measures in participants over a two-year period will help to establish sensitivity to change. The proposed research will benefit a wide range of studies aiming to assess or improve specific domains of cognition and general intellectual functioning in persons with ID.